Histamine and duodenal ulceration in renal transplant recipients.

Abstract

SUMMARY Six of 25 renal transplant recipients had a duodenal ulcer at endoscopy. Histamine concentration and the activity of histamine methyltransferase, the degrading enzyme of histamine, were measured in gastric mucosal biopsies obtained at endoscopy and compared with patients with duodenal ulcer but not undergoing transplant and with patients with an apparently normal stomach and duodenum. Histamine concentrations in the corpus (no ulcer, median: 151 nmol/g; DU, median: 122 nmol/g) and in the antrum (no ulcer, median: 118 nmoVg; with DU, median: 113 nmoVg) of renal transplant patients, irrespective of ulcer diagnosis, and in patients with a chronic duodenal ulcer (median corpus histamine: 137 nmollg and median antral histamine: 126 nmol/g) were not different from one another but significantly lower than the corresponding values in normal subjects (median corpus histamine: 241 nmoVg, p<001, and median antral histamine: 178 nmollg, p<0 05). Histamine concentration in the corpus was significantly higher than in the antrum in all three groups of patients (p<005). There were no significant differences in histamine methyltransferase activity in any of the groups studied. Mucosal histamine and histamine methyltransferase activity were significantly correlated in the corpus (p<O0O5) and antrum (p<002). Plasma concentration of histamine after transplant was higher in the patients who subsequently were discovered to have a duodenal ulcer (p<005). The occurrence of ulcer after transplantation was not related to the serum creatinine level. The uniform depletion of gastric histamine and increase in circulatory histamine after renal transplantation may be a factor in the pathogenesis of duodenal ulcer disease in this clinical situation.Patients with duodenal ulcer have depleted mucosal histamine stores in the stomach.' This depletion of histamine is associated with gastric hypersecretion, which is a prominent feature of duodenal ulcer disease. After treatment with cimetidine2 or vagotomy,3 mucosal histamine rises above normal control values, which parallels the reduction in gastric acid secretion. These observations lead to the suggestion that endogenous histamine may reflect the pathogenic states in the gastric mucosa of patients suffering from duodenal ulcer disease.-Renal transplant recipients are known to have an increased risk of developing peptic ulcer, which occurs in 6% to 22% of allograft recipients4'5 but the role of H2 receptor blockade in transplant recipients

Single nucleotide polymorphisms and haplotypes of histamine N-methyltransferase in patients with gastric ulcer

“…Obviously, our present study showed no significant difference between the GU cases and normal controls in frequencies of the HNMT alleles, genotypes, haplotypes and haplotype pairs. This observation, in accordance with the findings of some investigators [10,11,15], suggests that individual variation in HNMT activity might not contribute much to the susceptibility to GU. As a matter of fact, the released histamine in gastric mucosa is not only a risk factor for peptic ulcers by stimulating the acid secretion, but also has a gastroprotective effect by increasing the gastric blood Vol.…”

“…Previous studies on the HNMT activity in patients with peptic ulcer, however, have given conflicting results, with decreased [7 -9, 14], increased [5], and unchanged [10,11,15] mucosal HNMT activity having been all reported. As the HNMT activity in human tissues is predominantly regulated by inheritance [16,17], it is possible that gene polymorphisms of HNMT might play roles in susceptibility to some histamine-related diseases, such as asthma, allergy, peptic ulcers and neuropsychiatric disorders.…”

Pharmacokinetic Optimisation of the Treatment of Peptic Ulcer in Patients with Renal Failure*

“…When endoscopy was routinely performed after transplantation, duodenal ulcer prevalence was as high as 18 to 24%. [6,13,14] In those patients peptic ulcer was associated with a mortality rate of up to 34%. [12] Although the multifactorial pathogenesis of ulcers is poorly understood, it is generally believed that ulcerations develop when acid secretion and mucosal defensive and/or protective mechanisms are out of balance.l 15 ] A causative role is accepted for Helicobacter pylori in type B gastritis and H. pylori infection is regarded as a major factor in the development of peptic ulcer disease.l 16 ] We found that H. pylori was present in 34 to 47% of patients with renal failure compared with 54% of patients with normal renal function.l 17 ] Several reports have implicated nonsteroidal anti-inflammatory drugs (NSAIDs) as causative factors for gastric ulcers.…”

Histamine in Anaesthesia and Surgery: Causality Analysis

“…This work was systematically extended over the next 15 years (KUSCHE et al 1977a,b;THERMANN et al 1978;KUSCHE et al 1978KUSCHE et al , 1979ROHER et al 1982;Lorenz et al 1984b;DIETZ et al 1984;KUSCHE et al 1985;DOENICKE et al 1985;LORENZ and DOENICKE 1985a;STAHLKNECHT et al 1985;DIETZ et al 1988;LINDLAR et al 1989). Recently this approach was taken up very successfully by the Hammersmith group, mainly in cardiac and transplantation surgery (MARATH et al 1987(MARATH et al , 1988aHANSEN et al 1988;STEGER et al 1989;TIMONEY et al 1989). Hence it is now possible to demonstrate a large variety of situations in the operating theatre where free histamine appears in the circulation and to stimulate even more research in this almost endless field.…”